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Potassium Phosphate, Tribasic → 2-(4-(difluoromethoxy)-N-(1-(4-(pyrimidin-5-yl)phenyl)cyclobutyl)phenylsulfonamido) acetic acid

HRID 1951749
ノート
印刷プレビュー

反応式

HRID 1951749 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([N:12]([CH2:26][C:27]([OH:29])=[O:28])[S:13]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH:23]([F:25])[F:24])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[N:30]1[CH:35]=[C:34](B(O)O)[CH:33]=[N:32][CH:31]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C(O)CCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:24][CH:23]([F:25])[O:22][C:19]1[CH:20]=[CH:21][C:16]([S:13]([N:12]([CH2:26][C:27]([OH:29])=[O:28])[C:8]2([C:5]3[CH:6]=[CH:7][C:2]([C:34]4[CH:35]=[N:30][CH:31]=[N:32][CH:33]=4)=[CH:3][CH:4]=3)[CH2:11][CH2:10][CH2:9]2)(=[O:15])=[O:14])=[CH:17][CH:18]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 53373333HCID 53373333、化合物

生成物 1

HCID 533734692-(4-(difluoromethoxy)-N-(1-(4-(pyrimidin-5-yl)phenyl)cyclobutyl)phenylsulfonamido) acetic acid収率 16%

試薬・触媒・溶媒

2
HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 2631-Butanol溶媒

反応条件

温度
100 °C

実験手順

To a solution of 2-(N-(1-(4-bromophenyl)cyclobutyl)-4-(difluoromethoxy)phenylsulfonamido) acetic acid (20 mg, 0.041 mmol) in n-butanol (2 mL) was added pyrimidin-5-ylboronic acid (7.58 mg, 0.061 mmol), followed by potassium phosphate (17.32 mg, 0.082 mmol) and Pd2 dba3 (2.345 mg, 4.08 μmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (3.89 mg, 8.16 μmol). The mixture was degassed and flushed with argon and then shook at 100° C. for 3 h. The resultant mixture was filtered and the filtrate purified using Shimadzu prep HPLC employing an ACN/water and 0.1% TFA buffer with a Xterra column, 30 mm×100 mm, Gradient over 15 min; Starting conc: 10% B; Ending conc: 100% B. The solvent was removed in vacuo to give 3.3 mg (16% yield, 95% pure) of the title compound as a light gray solid. ESI-MS m/z 490 (MH+), 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.67 (q, J=10.07 Hz, 1H), 1.78-1.92 (m, 1H), 2.63 (t, J=8.70 Hz, 2H), 2.86 (d, J=2.44 Hz, 2H), 4.21 (s, 3H), 6.58 (t, J=75.00 Hz, 1H), 7.09 (d, J=8.55 Hz, 2H), 7.54 (d, J=8.24 Hz, 2H), 7.67 (dd, J=14.80, 8.70 Hz, 4H), 9.10 (s, 2H), 9.31 (s, 1 H).

後処理

  1. customThe mixture was degassed
  2. customflushed with argon
  3. filtrationThe resultant mixture was filtered
  4. customthe filtrate purified
  5. customover 15 min
  6. customThe solvent was removed in vacuo

出典と根拠

ORDレコード
ord-eaac1630d56f458e98af268a5c39d972
出典データセット
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08404741B2

反応ノート

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